Early use of tocilizumab in the prevention of adult respiratory failure in SARS-CoV-2 infections and the utilization of interleukin-6 levels in the management.

Respiratory failure in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection appears related to cytokine release syndrome that often results in mechanical ventilation (MV). We investigated the role of tocilizumab (TCZ) on interleukin-6 (IL-6) trends and MV in patients with SARS-CoV-2. In this longitudinal observational study, 112 patients were evaluated from 1 February to 31 May 2020. TCZ was administered followed by methylprednisolone to patients with >3L oxygen requirement and pneumonia severity index score ≤130 with computed tomography scan changes. IL-6, C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), D-dimer, and procalcitonin were monitored on days 0, 3, and 6 of therapy. Statistical analyses were performed with significance ≤0.05. Eighty out of 112 SARS-CoV-2-positive patients (45 males, 56.96%; 34 females, 43.04%) were included in this study. Seven patients expired (8.75%) and nine patients required MV (11.25%). Median IL-6 levels pre-administration of TCZ was 342.50 (78.25-666.25) pg/mL compared with post-administration on day 3 (563; 162-783) pg/mL (P < .00001). On day 6, the median dropped to 545 (333.50-678.50) pg/mL compared with day 3 (P = .709). CRP, ferritin, LDH, and D-dimer levels were reduced after TCZ therapy. Early use of TCZ may reduce the need for MV and decrease CRP, ferritin, LDH, and D-dimer levels. The sequential use of methylprednisolone for 72 hours seems to potentiate the effect and prolong the suppression of the cytokine storm. IL-6 levels may be helpful as a prognostic tool.

A Grape Seed Procyanidin Extract Ameliorates Fructose-Induced Hypertriglyceridemia in Rats via Enhanced Fecal Bile Acid and Cholesterol Excretion and Inhibition of Hepatic Lipogenesis.

The objective of this study was to determine whether a grape seed procyanidin extract (GSPE) exerts a triglyceride-lowering effect in a hyperlipidemic state using the fructose-fed rat model and to elucidate the underlying molecular mechanisms. Rats were fed either a starch control diet or a diet containing 65% fructose for 8 weeks to induce hypertriglyceridemia. During the 9th week of the study, rats were maintained on their respective diet and administered vehicle or GSPE via oral gavage for 7 days. Fructose increased serum triglyceride levels by 171% after 9 weeks, compared to control, while GSPE administration attenuated this effect, resulting in a 41% decrease. GSPE inhibited hepatic lipogenesis via down-regulation of sterol regulatory element binding protein 1c and stearoyl-CoA desaturase 1 in the fructose-fed animals. GSPE increased fecal bile acid and total lipid excretion, decreased serum bile acid levels and increased the expression of genes involved in cholesterol synthesis. However, bile acid biosynthetic gene expression was not increased in the presence of GSPE and fructose. Serum cholesterol levels remained constant, while hepatic cholesterol levels decreased. GSPE did not modulate expression of genes responsible for esterification or biliary export of the newly synthesized cholesterol, but did increase fecal cholesterol excretion, suggesting that in the presence of GSPE and fructose, the liver may secrete more free cholesterol into the plasma which may then be shunted to the proximal small intestine for direct basolateral to apical secretion and subsequent fecal excretion. Our results demonstrate that GSPE effectively lowers serum triglyceride levels in fructose-fed rats after one week administration. This study provides novel insight into the mechanistic actions of GSPE in treating hypertriglyceridemia and demonstrates that it targets hepatic de novo lipogenesis, bile acid homeostasis and non-biliary cholesterol excretion as important mechanisms for reducing hypertriglyceridemia and hepatic lipid accumulation in the presence of fructose.

Glenohumeral instability associated with Buford complex.

Buford complex is described as a normal anatomical variant of the anterosuperior part of the glenoid consisting of the absence of the anterosuperior labrum with the presence of a cord-like middle glenohumeral ligament. Traditionally, reattachment to the glenoid has been discouraged. We present a case of a Buford complex associated with glenohumeral instability. The patient was operated for recurrent instability without a preoperative diagnosis of Buford complex. The diagnosis was made during shoulder arthroscopy and reattachment to the glenoid was performed with a satisfactory outcome. Here, we discuss the relationship of the Buford complex with intraarticular pathology and the surgical treatment in cases when this variant is associated with instability.